The purpose of the proposed research is to explore systematically the capabilities of various tissues (liver, adrenal, kidney, lung, brain, placenta and bone marrow) to metabolize a number of drug substrates. Drug biotransformation processes to be investigated include oxidation, reduction and conjugation (glucuronidation, sulfation, acetylation, and glycine coupling). Studies will be conducted at various stages of pre- and postnatal development. The importance of such studies is indicated by the possible relationships of drug metabolic processes during development to: abnormal effects of drugs upon the pregnant woman and fetus resulting in abortions, congenital malformations and increased perinatal mortality and morbidity. Determination of the acute and chronic sensitivity of these drug metabolizing enzyme systems to administration of hormones and drug substances (known to alter enzyme activity) and to modification of the external environment will be made. Emphasis will be placed upon nutritional factors. In vitro findings will be correlated with in vivo observations of pharmacologic effect. The information which will be provided by these investigations should afford a better understanding of effects of drugs on the fetus, newborn infant, and older child, as well as on the pregnant female. The application of this knowledge will establish a more rational basis for optimal therapeutics in the developing organism. In addition, elucidation of drug effects upon embryonic and fetal development will lead to an understanding and hence prevention of birth defects.